14. Haemostasis 2 Flashcards
Normal haemostasis
Balance between fibrinolytic factors and anticoagulant proteins + coagulation factors and platelets
What causes bleeding disorders?
Too little pro-coagulant factors (VIII,IX,XI)
Too many anticoagulant factors
List 4 characteristics of abnormal bleeding
‘Spontaneous’
Out of proportion to the trauma/injury
Unduly prolonged
Restarts after appearing to stop
What clinical feature is common to all bleeding disorders?
Easy bruising
Give 3 examples of significant bleeds
Nosebleed not stopped by 10 mins compression
Cutaneous haemorrhage
Prolonged (>15 mins) bleeding from trivial wounds
List 3 defects of primary haemostasis
Deficiency or defective:
Collagen (steroid therapy, age, scurvy)
Von Willebrand factor (genetic disease)
Platelets (aspirin, thrombocytopenia)
What happens to patients with Von Willebrand factor deficiency?
Damaged vessel wall
But no VWF, so platelets can’t stick (as move too fast)
Patient bleeds as can’t form primary haemostatic plug
(bleed from outset)
Describe the pattern of bleeding of a defect in primary haemostasis.
Immediate Easy bruising Nosebleeds (prolonged: >20 mins) Gum bleeding (prolonged) Menorrhagia (anaemia)
What is a characteristic feature of thrombocytopenia?
Petechiae (bleeding spots)
What is the main role of primary haemostasis?
Formation of an unstable platelet plug
(through platelet adhesion and aggregation)
Limits blood loss and provides surface for coagulation
What is the main role of secondary haemostasis?
Stabilisation of the platelet plug with fibrin
Blood coagulation
Stops blood loss
Why is there a lag between the administration of a tissue factor trigger and the thrombin burst?
This is when cofactors and clotting factors are synthesised.
Describe the cause of haemophilia A
There is insufficient FVIII
Thrombin generation “boost” doesn’t happen
Failure of thrombin generation
Failure to generate fibrin mesh to stabilise platelet plug
Attempted haemostasis in haemophilia A
Primary haemostatic plug forms so initially stop bleeding, but it doesn’t get stabilised so falls apart
Defects of secondary haemostasis
Deficiency or defect of coagulation factors
Poor thrombin burst, poor fibrin mesh
Genetic defects of secondary haemostasis
Haemophilia: FVIII or FIX deficiency
List 4 acquired disorders of secondary haemostasis
Liver disease (most coagulation factors are made in the liver)
Drugs (warfarin: inhibits synthesis, others block function)
Dilution (results from volume replacement: when not enough plasma is replaced)
Consumption (DIC)
What is DIC an abbreviation for? What is DIC?
Disseminated intravascular coagulation
Generalised activation of the coagulation- expression of tissue factor inside vasculature
Consumes and depletes clotting factors and platelets
Activates fibrinolysis- depletes fibrinogen
What is DIC associated with?
Sepsis
Major tissue damage
Inflammation
What are the consequences of DIC?
Widespread bleeding
Deposition of fibrin in vessels causes organ failure
Describe the pattern of bleeding of defects in secondary haemostasis.
Delayed (after primary haemostasis) Prolonged Bleed deeper into joints and muscles. Not from small cuts (primary haemostasis is fine) Nosebleeds rare Bleeding after trauma/ surgery Easy bruising
What is the hallmark of haemophilia?
Haemarthrosis: bleeding into joints
Defects in fibrinolysis prevalence
Not so common
What will excess fibrinolytic activity cause?
Excess bleeding
State 2 defects of clot stability
Excess fibrinolytic (plasmin, tPA) Deficient antifibrinolytic (antiplasmin)
What causes excess fibrinolytic activity (plasmin, TPA)?
Therapeutic administration (given to people with strokes to break down blood clot) Some tumours
What causes deficient antifibrinolytic activity (antiplasmin))?
Antiplasmin deficiency (genetic)
What causes anticoagulant excess?
Usually therapeutic administration e.g. Heparin (which activates antithrombin)
Describe the characteristics of thrombosis
Excess FVIII Increased procoagulant activity Deficient anticoagulant activity Blood clot should not have been formed, unnecessary, not preceded by bleeding Blood vessel intact with clot inside it Pathological clot formation
What are the effects of thrombosis?
Obstructed flow of blood
Embolism (migration of the thrombus)
What may obstructed flow in an artery or vein cause?
Artery: stops blood flow to organ/ area of tissue, usually more immediately serious e.g. MI, stroke, limb ischaemia
Vein: blood can usually still return to heart via a different route. May cause pain/ swelling
What may arterial emboli cause?
Stroke
Limb ischaemia
What may venous emboli cause?
Pulmonary embolism (shortness of breath, chest pain, sudden death)
Deep vein thrombosis
Venous return of blood obstructed
painful, swollen leg
How does risk of thrombosis change with age?
Increases
What are the 4 consequences of thromboembolism?
Death
Recurrence
Thrombophlebitic syndrome
Pulmonary hypertension
List 3 possible contributory factors to thrombosis
Genetics
Acute stimulus
Effect of age, illness, medication
What are the 3 components of Virchow’s triad?
Blood hypercoagulability (dominant in venous thrombosis) Vessel wall injury (dominant in arterial thrombosis) Stasis (contributes to both)
Increased risk of Venous thrombosis: Blood
Deficiency of anticoagulant proteins e.g. Antithrombin
Increased coagulant proteins e.g. FVIII
Increased risk of Arterial thrombosis: vessel wall
Many proteins active in coagulation are expressed on the surface of endothelial cells e.g. Thrombomodulin
Expression is altered in inflammation e.g. infection
Increased risk of thrombosis: Flow
Reduced flow (stasis) increases the risk of venous thrombosis e.g.: surgery, fracture
What do people with Thrombophilia have an increased tendency of?
Increased tendency of thrombosis
What are the signs of thrombophilia?
Thrombosis at young age
Idiopathic thrombosis
Multiple thromboses
Thrombosis whist anticoagulated
Which 4 conditions will alter blood coagulation, vessel wall and/ or flow to precipitate thrombosis?
Pregnancy
Malignancy
Surgery
Inflammatory response
What is lysing thrombi not often a method of treatment?
There is a high risk of bleeding
What is the main approach to treating thrombi?
Limit recurrence/ extension/ emboli:
Increase anticoagulant activity e.g. heparin
Decrease procoagulant factors e.g. Warfarin
Inhibit procoagulant factors
